First Author | Pignon JC | Year | 2013 |
Journal | Proc Natl Acad Sci U S A | Volume | 110 |
Issue | 20 | Pages | 8105-10 |
PubMed ID | 23620512 | Mgi Jnum | J:197339 |
Mgi Id | MGI:5492195 | Doi | 10.1073/pnas.1221216110 |
Citation | Pignon JC, et al. (2013) p63-expressing cells are the stem cells of developing prostate, bladder, and colorectal epithelia. Proc Natl Acad Sci U S A 110(20):8105-10 |
abstractText | The tumor protein p63 (p63), and more specifically the NH2-terminal truncated (DeltaN) p63 isoform, is a marker of basal epithelial cells and is required for normal development of several epithelial tissues, including the bladder and prostate glands. Although p63-expressing cells are proposed to be the stem cells of the developing prostate epithelium and bladder urothelium, cell lineages in these endoderm-derived epithelia remain highly controversial, and rigorous lineage tracing studies are warranted. Here, we generated knock-in mice expressing Cre recombinase (Cre) under the control of the endogenous DeltaNp63 promoter. Heterozygote DeltaNp63(+/Cre) mice were phenotypically normal and fertile. Cre-mediated recombination in DeltaNp63(+/Cre);ROSA26(EYFP) reporter mice faithfully recapitulated the pattern of DeltaNp63 expression and were useful for genetic lineage tracing of DeltaNp63-expressing cells of the caudal endoderm in vivo. We found that DeltaNp63-positive cells of the urogenital sinus generated all epithelial lineages of the prostate and bladder, indicating that these cells represent the stem/progenitor cells of those epithelia during development. We also observed DeltaNp63 expression in caudal gut endoderm and the contribution of DeltaNp63-positive cells to the stem/progenitor compartment of adult colorectal epithelium. Because p63 is a master regulator of stratified epithelial development, this finding provides a unique developmental insight into the cell of origin of squamous cell metaplasia and squamous cell carcinoma of the colon. |